Ultraviolet (UV) radiation is a very prominent environmental toxic agent. Particularly, UVB (280–320 nm – short wave) wavelength penetrates the epidermis and is completely absorbed in the upper dermis, whereas UVA (320–400 nm - long wave) penetrates to the deeper dermis. UVA is a relatively weak carcinogen than UVB because of its weak strength as a tumor initiating agent. UVB exposure elicits adverse effect which includes sunburn, basal and squamous cell carcinoma, melanoma, cataracts, photoaging of the skin and immunosuppression. Increased ozone depletion and modern lifestyle has increased the amount of UV exposure, and this consequently led to a surge in the incidence of skin cancer. UVB-irradiation acts as both tumor initiator and tumor promoter in animal models. UVB-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. Variety of cellular changes, which includes activation of transcription factors and protein kinases were altered during acute and chronic UVB-exposure. All these events leads to skin cancer development involving DNA damage, inflammation, immunosuppression, epidermal hyperplasia, cell cycle dysregulation, depletion of antioxidant–defenses, and reactive oxygen species generation. An epidemiological study shows that human beings consuming varieties of vegetables and fruits are protected from UVB induced carcinogenesis. In the recent years, number of experimental evidences showed that natural nutraceuticals and phytoceuticals are vital targets for UVB-mediated cellular and molecular events and prevents cellular milieu from UVB mediated health effects. In this review, we have discussed the current progress in the study on UVB-mediated signaling that can be exploited as targets for phytochemicals.

The discovery of ultraviolet (UV) radiation and its properties was a gradual process that spanned three centuries and involved scientists from many countries.[1][Table 1] depicts the discovery of UV radiation through various breakthrough events. The sun emits UV radiation, which covers a small part of the electromagnetic spectrum from 400 nm to 100 nm. Within the UV portion of the spectrum, the biological effects of the radiation vary significantly with wavelength range. Sun light emits UV radiation in the UVA (320–400 nm), UVB (280–320 nm), and UVC (200–280 nm) bands, but because of absorption in the atmosphere's ozone layer, 99% of the UV radiation reaches the earth's surface is UVA. UV radiation is a very prominent environmental toxic agent. UVB radiation (wavelengths between 280 and 320 nm) is partially absorbed by the ozone layer and the remaining portion that reaches the earth can cause severe damage on biological organisms, while UVA (wavelengths >320 nm) is not absorbed by ozone layer and comparatively is not damaging to biological organisms.[2]

UVB radiation, comprising approximately 5–10% of the entire spectrum of UV radiation reaching the surface of the earth is characterized by a relatively high energy and responsible for the most important biological effects including sunburn, erythema, pigmentation, Vitamin D3 synthesis, immunosuppression, inflammation, photoaging, and carcinogenesis. UVB is absorbed in the stratum corneum of the skin by cellular chromophores. Effected factors in the skin are melanin, cellular DNA, urocanic acid, proteins, lipids, and amino acids. UVB directly damages the DNA strand, resulting in the formation of pyrimidine dimers and distortion of repair mechanisms, which lead to mutations. The reactions induced by UVB radiation are immediate, resulting in the release of inflammatory mediators (e.g., histamine, serotonin, and prostaglandins [PGs]), which lead to dilation of capillaries and the development of erythema and edema. UVB easily penetrates through water and quartz glass. However, these rays are filtered through clouds and windowpanes. Greatest ray intensity is reached during the summer, between the hours of 10 am and 5 pm.[3]

High Ultraviolet Exposure Regions Worldwide

The ozone layer acts as earth's sunscreen, filtering harmful UV radiation from the sun. However, in areas where the ozone layer is compromised, more UV rays hit the earth, which means more skin damage from sun exposure. With its proximity to the South pole's seasonal “ozone hole,” Australia is the skin cancer capital of the world. High UVB exposures occur in nearby regions at both poles, including some regions where people live, such as Scandinavia, most of Europe, Canada, New Zealand, Australia, South Africa, and the Southern region of South America. Exposures get especially high in regions of elevated altitude, such as in the Andes Mountains, and in places that are relatively free of clouds at certain times of the year, such as South Africa and Australia during their summer (December to February). In July, very high exposures appear over the Sahara, Saudi Arabia, South-Western United States, and the Himalayan Mountain regions in Northern India and Southern China. The equatorial regions have their maximum exposure in the spring and autumn, with higher values during the autumn due to decreased cloud cover. The table shows that the effect of UVB exposure in various region in the worldwide [Table 2].

The incidence of both cutaneous malignant melanoma (CM) and nonmelanoma skin cancer (NMSC) has been increased precipitously in fair-skinned populations over the past five decades.[4] Epidemiological and clinical studies reported that Australia and New Zealand are the countries with highest incidence of skin cancer in worldwide observed due to intensive UV radiation exposure.[4],[5] The lifetime risk of skin cancer is highest in New Zealand and Australia (3.6%) compared to other parts of the world. In Europe, incidence rates are particularly high in the Nordic countries, Switzerland, the Netherlands, the Czech Republic and Slovenia, while Mediterranean countries, Baltic and Eastern European countries, and tend to have lower rates.[5] In most parts of Europe, the incidence rates are higher among women than among men. Recent findings indicate a uniformly increasing trend in European countries over the last decade, with the highest increase seen among older ages with strong North-to-South and East-to-West variation (higher incidences in the North and East). However, for Norway, France, and Iceland, CM incidence rates are being leveled, most notably in young people aged 25–44 years. Nonetheless, incidence rates continue to rise irrespective of age in most European populations, and predictions suggest a continuation of this trend.[6] Incidence rates and time trends are difficult to estimate for NMSC, as they are often either not registered at all or incompletely covered by population-based cancer registries.[5] Of the specific NMSC types, squamous cell carcinoma (SCC) is included in relatively few cancer registries. Actinic keratosis is considered by some to be in situ SCC and to our knowledge is not registered by any population-based cancer studies. All age groups are affected by skin cancer with an average age of onset of 55, but the younger age group (15–30) and older age group (60+) are more sensitive to increasing UV radiation.[6] In spite of progress in treatment, skin cancer is one of the most common human cancers with >1 million new cases diagnosed each year, accounting for about 40% of all new cancer cases in the USA (http://www.cancer.org).[8] In the last 30 years, the rate of newly diagnosed melanomas has tripled in men and more than doubled in women in the U.S.[9] Melanoma is most common in parts of the world where fair-skinned whites live in a sunny climate near the equator. Whites in Hawaii and the South-Western U.S. also have a high incidence of melanoma, about 20–30 cases per 100,000 individuals annually. Yet skin cancer is uncommon in African-American individuals, with an annual age-adjusted incidence of only 0.9% of that of whites.[7]

UVB radiation has strong genotoxic effects to produce directly DNA damage, induce mutations and cause development of skin carcinogenesis. UV produces specific DNA damage such as cyclobutane pyrimidine dimers and pyrimidine (6–4) pyrimidone photoproducts and these photo lesions are assumed to cause UV specific mutations. In addition, UVB radiation indirectly induces oxidative stress through the generation of reactive oxygen species (ROS) by activating small molecules such as melanin, tryptophan, riboflavin, and porphyrin which can then activate cellular oxygen. These ROS mediated DNA damage can produce oxidative base damage such as 8-hydroxyguanine.[10] UVB radiation activates several predominant pathways which are regulated by photo-oxidative damage such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB), and janus kinase (JAK)/signal transduction and activation of transcription (STAT) signaling etc.[11] Activation of cell surface receptors by UV irradiation stimulates a signal which involves MAPK family members, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, leading to the activation of the activator protein-1 (AP-1) and NF-κB transcription factor family members.[12] Both AP-1 and NF-κB regulate the expression of a number of genes involved in the UV response implicated in inflammation, angiogenesis, photoaging and skin cancer. UVB radiation has been involved in impairing the synthesis of collagen and induces the expression of matrix metalloproteinases (MMPs) specifically regulated by AP-1 resulting in the photoaging.[12]

The JAK family consists of nonreceptor tyrosine protein kinases and plays a critical role in cell survival, proliferation, differentiation, and apoptosis. JAK kinase is required for the tyrosine phosphorylation of STAT3, which is activated by cytokines and growth factors. STATs are DNA-binding transcriptional factors,[13] and STAT1, STAT3, and STAT5 are frequently activated in human cancers, with a higher incidence of abnormal STAT3 activation in almost all tumors studied.[14] STAT3 is constitutively activated in a number of human malignancies, including breast cancer, lung cancer, melanoma, brain tumors, prostate cancer, and pancreatic adenocarcinoma. Therefore, the JAK1 – STAT3 pathway has been suggested as play a critical role in cell transformation and carcinogenesis.

UVB-radiation primarily generates ROS that play a key role in mediating most of the biological responses that can activate a number of signaling pathways as well as cause lipid peroxidation in cellular membrane resulting in oxidative damage to DNA and proteins.[15] Adverse effects of UVB mediated erythema, edema and hyper proliferative epithelial responses which are known for their representative inflammatory markers, and play important role in skin tumor promotion.[16] Skin exposure to UVB-radiation generates an immunosuppressive condition that is mainly mediated by interleukin-10 (IL-10) and IL-4, molecules which generate a significant amount of CD4+ CD25+ regulatory T-cells.[17] UVB induced inflammatory response is mainly mediated by several molecules: Tumor necrosis factor-α (TNF-α); PG E2 (PGE2) produced by cyclo-oxygenase enzymes (COX); nitric oxide (NO) produced by NO synthase enzymes (NOS) and other cytokines such as IL-6 and IL-1.[18] These inflammatory factors are produced mostly in keratinocytes, the main cells of the epidermis and major target of UVB-radiation and they are regulated predominantly by the NF-κB.[19] UVB radiation induced COX-2 and PGE2 expression has been related to the pathological inflammation and cancer.[16]

Ultraviolet-B Radiation-Mediated Photocarcinogenesis

UVB radiation acts as both tumor initiator and tumor promoter in several animal models. UV-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. It has been reported that a large number of cellular changes, including activation of transcription factors and protein kinases are accelerated by an exposure of UV-irradiation. Solar UVB-radiation induced skin carcinogenesis is a multistage process involving three distinct stages exemplified by initiation, promotion, and progression [Figure 1]. Each of these stages is mediated by means of alterations in various cellular, biochemical, and molecular changes. Tumor initiation, the first step in the photocarcinogenesis process, involves genetic alterations that ultimately leads to DNA mutation in normal cells and is essentially an irreversible process. Tumor promotion involves clonal expansion of initiated cells by alterations in signal transduction pathways and is considered to be reversible. Tumor progression involves malignant transformation of papillomas to carcinomas.[20],[21] As initiation process occurs rapidly and therefore strategies to prevent initiation process by intervention are difficult to envision. The best approach to intervene photocarcinogenesis might be in the tumor promotion phases of carcinogenesis as these steps are the slow and rate limiting stages.

Photochemoprevention is an emerging interest in the use of naturally occurring antioxidants for their therapeutic usage.[22] Early study demonstrates that phytochemicals are considered as potential therapeutic agents against a wide range of ailments including cancer, diabetes, cardiovascular dysfunction, inflammatory diseases and photoaging.[23] One approach to protecting humans from the harmful effects of UV-irradiation is to use active photoprotectives. In recent years, naturally occurring compounds have gained considerable attention as protective agents. Vitamins C, E, and β-carotene have been incorporated into many skin care products for instance. Numerous animal and in vitro studies have demonstrated the photochemopreventive effects of naturally occurring botanical phenolic compounds by ingestion or applied to the skin, many occurring in foodstuffs, e.g. resveratrol from grapes,[24] delphinidin from pomogranates,[25] (-)-epigallocatechin-3-gallate (EGCG) from green tea,[26] genistein from soybeans [27] as well as complex extracts from plants, e.g., extracts of beetroot,[28] green tea,[29] pine bark [30] and grape seeds [Table 3].[31] Clinical trials have begun, in which some compounds are being investigated in humans for the prevention of various cancer types, such as genistein for breast cancer and pancreatic cancer, resveratrol for colon cancer, curcumin for pancreatic cancer and colorectal cancer and EGCG for cervical cancer.[32] From these studies, it is clear that there is a potential for phenolic phytochemicals to be used as sunscreens and photoprotective skin care products [Figure 2].

Several experiments have elucidated the protective effect of natural products against UVB radiation induced damages in cells, tissues, animals, and humans. Photochemoprevention is the use of synthetic or natural substances that prevent, holdup or reverse the damages caused by UV radiation.[33] The photochemoprevention involves substances which are capable of UV absorbing ability and act as sunscreen to prevent UVB mediated adverse effects such as sunburn, erythema, inflammation, skin aging, and skin cancer. In addition, polyphenolic compounds with antioxidant activities protect against photo-oxidative damage on DNA, lipids and proteins.[23] In recent years, epidemiological and experimental studies have focused on a wide variety of natural products that provide protection against formation of skin cancer because it can modulates a variety of cellular functions induced by the UV radiation. Thus, use of natural products as photochemopreventive agents can contribute in reducing the risk of skin cancer in combination with changes in lifestyle, diet, and products for skin care.[34] This review presents the main molecular mechanisms of various phytochemicals in the chemoprevention of skin cancer. A wide variety of dietary flavonoids or phenolic substances can reduce the risk of noncommunicable diseases via antioxidant actions.[35] Many of plant derived phenolic compounds are secondary products of plant polyphenols metabolism possesses diverse pharmacological properties including antioxidant, anti-inflammatory, antimutagenic and anticancer activities. These substances have been proved to block carcinogenesis and to inhibit tumor growth both in vitro and in vivo models.[33]

UVB induced phosphorylation of signaling pathways (MAPK) has been shown to activate several transcriptional factors which leads to regulates inflammation, cell proliferation, aging, and carcinogeneic events.[31] Botanical antioxidants have been shown to be associated with considerable attention for reduced incidence of photocarcinogenesis and photoaging because antioxidant nature of phytochemicals inhibits several transduction pathways [Table 3].[36] Katiyar and Mukhtar, 1996; Katiyar et al., suggest that inhibition of UVB-induced H2O2 and subsequently, H2O2-mediated phosphorylation of MAPK signaling by EGCG may be associated with the inhibition of UVB-induced markers of carcinogenesis and subsequently cancer induction as well in animal models.[37],[38] Isoflavone extracts prepared from soybean cake showed better antioxidant activities than genistein, daidzein, genistin, and daidzin. These extracts inhibited UVB induced keratinocyte death, release of hydrogen peroxide (H2O2), and UVB induced MAPK phosphorylation.[39] Several authors suggest that significant inhibition of UVB-induced phosphorylation of MAPKs by grape seed proanthocynadin (GSPs) might be responsible for their inhibitory effects on the activation of transcription factor NF-κB. Therefore, the inhibition of the MAPK and NF-κB signaling pathways could potentially be utilized by GSPs to activate antioxidant responsive element-dependent genes.

Numerous studies have postulated that dietary phytochemicals has effects of chemoprevention and treatment in skin cancer through the regulation of the nuclear factor-erythroid related factor-2,[40] activation MAPK, IκB degradation, NF-κB activiation, AP-1 activation, and COX-2 expression.[41] Previously, Katiyar and Mukhtar demonstrated that topical application of major green tea polyphenol EGCG (3 mg/mouse/3 m 2 of skin area) to C3H/HeN mice, before a single dose of UVB (90 mJ/cm 2) irradiation, decreases hydrogen peroxide and NOS-expressing cells, and inhibits hydrogen peroxide and NO production in both dermis and epidermis.[42] Silymarin, a group of flavanol extracted from the seeds of Silybum marianum or milk thistle and it has shown to be strong antioxitant in nature. Topical application of silymarin protects mouse skin against UVB induced suppression of contact hypersensitivity response to contact sensitizer dinitrofluorobenzene and infiltration of inflammatory leukocytes which are responsible for the generation of oxidative stress.[43] The treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine IL-10 producing cells and its production.[43] Silymarin inhibits photocarcinogenesis through inhibition of UVB-induced oxidative stress, inflammation, and suppression of immune system.[44],[45],[46] Lutein is xanthophylls, naturally occurring carotenoids and it has been synthesized only by plants and like other xanthophylls is found in high quantities in green leafy vegetables. Dietary supplementation of lutein reduces tissue swelling induced by UVB radiation and inhibits the UVB induced immunosuppressive effects. This study also suggests that lutein was found to accumulate in the skin following diet supplementation and decreases the production of ROS in skin following UVB.[47]

Ornithine decarboxylase (ODC) is an important enzyme that catalyzes the cellular polyamine biosynthesis, i.e., the formation of putrescine from ornithine. It has been associated with cellular transformation as well as cell cycle regulation.[24] COX-2 is another inflammatory mediator which is involved in synthesis of PGE2 from arachatonic acid in the skin. The enhanced expression of ODC and COX-2 during the course of UVB exposure plays a key role in carcinogenesis by contributing to uncontrolled proliferation of damaged cells that ultimately form tumors.[48] Oral feeding of green tea polyphenol to hairless mice, followed by irradiation with UVB, resulted in significant protection against UVB radiation-mediated cutaneous edema; depletion of the antioxidant-defense system in the epidermis; induction of epidermal ODC and COX-2 enzyme activities that play an important role in cutaneous inflammation and tumor promotion.[49] In addition, the UVB induced COX-2 protein expression is blocked by treatment with apigenin in UVB irradiated keratinocytes [50] and there are also reports that apigenin downregulates COX-2 expression in macrophages.[51],[52] Apigenin also enhances UVB radiation induced apoptosis, affecting both intrinsic and extrinsic pathways.[53] Recently, we reported that caffeic acid, a major phenolic acid inhibits COX-2, IL-6, TNF-α, and NF-κB expression which activates anti-inflammatory gene PPARγ in UVB exposed mouse skin.[54] Moreover, ferulic acid a precursor of caffeic has been shown to inhibit the expression of IL-6, TNF-α, and inducible NOS (iNOS) in UVB mediated mice skin thereby preventing photocarcinogenesis.[55] Pal et al. suggest that topical application of fisetin to SKH-1 mice after UVB exposure results in a significant decrease in leukocyte infiltration, inflammatory mediators (MPO, COX-2 and PGE2), inflammatory cytokines (TNF-α, IL-1b, IL-6) and proliferation markers (proliferating cell nuclear antigen [PCNA] and cyclin D1).[56] In addition, fisetin inhibited PI3K/AKT/NF-κB signaling, which is involved in UVB-induced inflammation, cell survival and proliferation. We also reported that sesamol inhibited UVB radiation induced activation of TNF-α and NF-κB inflammatory signaling in a dose-dependent manner. TNF-α is an important mediator involved in the UVB induced inflammatory reactions. Further, it activated NF-κB, a dominant transcription factor, responsible for inflammation.[57] Once activated, NF-κB binds to DNA and transcripts various proinflammatory genes, including cytokines and iNOS.[58]

Pomegranate fruit extract (PFE) protected against UVB mediated skin tumorigenesis in mouse model, at least in part, by modulating transcription factors STAT3, NF-κB and hypoxia-inducible factor-1α leading to decrease in inflammatory and angiogenic responses, and provide a molecular basis for its photochemopreventive effect.[59] In addition, silibinin also documented that reduction in phosphorylation of STAT3 (Tyr705) and NF-κB/p65 in UVB exposed mice models.

UVB radiation induced skin photoaging is another hallmark event for developing skin carcinogenesis. The clinical characteristics of UVB mediated photoaging skin have been known as skin have known coarse wrinkles, laxity, irregular pigmentation, and a leathery appearance.[60] The characteristics are very important for development of skin carcinogenesis. Botanical extracts and dietary phytonutrients appear to be effective antiphotoaging and anti-photocarcinogenic agents. In the previous studies, polyphenol rich extracts of Coffea arabica[19] and Terminalia catappa L.[61] prevented skin cells from UVB-induced photoaging by inhibiting the activation of MAPKs and MMPs. In addition, obovatol from magnolia extract has been shown to inhibit MMP-3 in UVB-irradiated human fibroblasts;[62],[63] Bog blueberry anthocyanins showed the protection against UVB-induced skin photoaging by blocking collagen destruction and inflammatory responses via transcriptional mechanisms of NF-κB and MAPK signaling.[64] We examined biomarkers of collagenolytic MMPs. The expression and secretion of both MMP-2 and MMP-9 were markedly decreased in mice applied with sesamol. Similar to our findings, sesamol significantly attenuated TNF-α- and IL-1 β-induced gelatinolysis and expression of MMP-9, MMP-1, and MMP-13 stimulated by phorbol 12-myristate 13-acetate.[65] Further, treatment of EGCG, a major polyphenolic constituent of green tea, has been shown to reduce UV induced skin damage (roughness and sagginess) and protected from the decrease of dermal collagen in hairless mouse skin, and also blocked the UV-induced increase of collagen secretion and collagenase mRNA level in fibroblast culture.[66] Pretreatment of human skin with PFE resulted in inhibition of UVB-induced phosphorylation of c-Jun, protein expression of c-Fos, and various MMPs protein expression.[67] Based on the above demonstration, naturally occurring phytochemicals are strongly prevents skin photoaging by exposure of UVB radiation.

Apoptosis is a regulated form of cell death and a multi-factor-related process, including gene expression and mutation. We observed increased ROS levels, DNA damage, and lipid peroxidation products during UVB-exposure in human diploid fibroblasts (HDF-a). Kulms and Schwarz indicated that DNA damage, ROS generation, and lipid peroxidation contributes to UVB-induced apoptosis in different ways. UVB-induced apoptosis is a highly complex process involving the extrinsic and intrinsic pathways.[68] We noticed up-regulated Bax, p53, Caspase-3, and downregulated Bcl-2 protein expression in UVB-irradiated HDF-a. The balance between proapoptotic (e.g. Bax, Bak and Bid) and antiapoptotic members of the Bcl-2 protein family (e.g. Bcl-2 and Bcl-XL) determines whether apoptosis is promoted or prevented.[44] Number of studies indicated the critical role of p53 in the apoptotic process in UVB-irradiated cells.[44],[69],[70]

EGCG hampers UVB-induced apoptotic signaling in human dermal fibroblasts.[71] Further, genistein, a soybean phytochemical, protects HDF-a against UVB-induced senescence-like state in a dose-dependent manner.[72] In HaCaT keratinocytes, chrysin can ameliorate various kinds of skin damage caused by UVA and UVB, including apoptosis, ROS overproduction, COX-2 induction, and downregulation of aquaporin. The efficiency and safety of topical application of chrysin have been confirmed in animal studies.[73] Soy isoflavone extracted from soybean cake prevented human keratinocyte apoptosis, attenuated the level of erythema and transepidermal water loss, reduced the epidermal thickness, and increased the catalase activity and inhibit COX-2 and PCNA expression in response to UVB exposure.[74]

Chemopreventive effects are modulated by two major events: Inhibition of cell proliferation and induction of apoptosis.[75] Chilampalli et al. indicate that honokiol induced apoptosis by both extrinsic and intrinsic pathways, significantly up regulating caspase-8, caspase-9, caspase-3 and PARP cleavage, which is involved in DNA fragmentation and apoptosis.[76] DNA fragmentation is a hallmark of apoptosis which commits cell to die. Our results suggest that honokiol inhibit UVB-induced skin carcinogenesis by inducing apoptosis and DNA fragmentation leading to apoptosis. Previously, quercetin induces c-Fos expression through activation of p38 and cAM presponsive element binding protein, and also potentiates UVB-induced c-Fos expression in human keratinocyte cell line, HaCaT. This cellular events important for the promotion of tumor development. Pretreatment of JB6 cells with quercetin reduced UVB-induced phosphorylation of MAPK, transactivation of AP-1 and NF-κB. This study suggests that quercetin contributes to the inhibition of neoplastic transformation by blocking activation of the cellular signaling pathway.[77]

Conclusion

Chronic exposure of UV radiation is associated with a variety of harmful effects to skin cancer. Many synthetic sunscreen agents are available in the market with certain limitation according to their potential for generating photoreaction adducts and may consequently create adverse effects on human skin. Natural compounds may work in various ways such as stimulate the immune response, induce gene suppression, block oxidative damage to DNA, etc. Accumulated data consistently support the view that many agents, with antioxidant properties, exert anti-inflammatory and anticarcinogenic effects in skin. This suggests the possibility that specific agents might be used to target defined and established molecular events for the prevention and treatment of UV radiation induced skin disorders. Skin care products supplemented with botanicals may be an effective approach for reducing UVB-generated ROS-mediated photodamage, inflammatory responses, DNA damage, and skin cancer. There is a possibility to develop potential photoprotective, photochemopreventive, anti-inflammatory, and antiphotoaging agents from natural medicinal compounds against UVB induced pathological conditions.

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